Radiation therapy is one of the cornerstones in the therapy of brain tumors. Though able to prolong functional and overall survival, its use is limited by its ability to also injure the normal central nervous system tissue around the neoplasm at the high doses necessary to truly limit tumor growth. Pentobarbital has been shown to decrease the extent of brain injury in certain models of cerebral ischemia and hypoxia. In patients harboring malignant gliomas it preferentially decreases the cerebral metabolic rate, as measured by position emission tomography, in normal brain parenchyma as compared to adjacent tumor tissue. Rats subjected to a range of doses of x-irradiation with or without pentobarbital anesthesia, had significantly better survival in the presence of pentobarbital over a range of 30 to 90 Gy with the maximally protective dose being 60 mg/kg. A suggestion as to the mechanism of this effect is given by the similar extent of radioprotection seen with diazepam and alphaxalone, compounds known to enhance GABA binding, though by subtly different mechanisms. Other methods of producing general anesthesia, e.g. ketamine, or producing hypometabolism, e.g. hypothermia give no radioprotection and suggest that in general terms are the mechanisms of radioprotection induced by pentobarbital. The use of pentobarbital in the x-irradiation of tumor bearing rats significantly enhanced their survival over treatment with x-irradiation alone. This suggests that pentobarbital's radioprotective is selective for normal tissue and does not protect tumor.
